Work

Hofbauer Cells in Pregnancies Complicated by Gestational Diabetes Mellitus and Pathological Fetal Growth

Year: 2026

Type: article

Abstract: PROBLEM: Gestational diabetes mellitus (GDM) increases the risk of large-for-gestational-age (LGA) birth and long-term cardiometabolic complications in offspring, particularly in males. These outcomes are associated with altered placental vascularisation, but the underlying mechanisms remain poorly defined. Hofbauer cells (HBCs) are fetal-origin macrophages located in the villous stroma with established roles in immune regulation and vascularisation. METHOD OF STUDY: This study investigated whether HBC abundance and phenotype are associated with fetal growth, fetal sex, and placental vascularisation in term placentae from non-GDM and GDM pregnancies. Pan-macrophage (CD14, CD68), HBC-enriched (FOLR2, VSIG4), M1 (CD86), and M2 (CD163, MRC1) markers were assessed by RT-qPCR and quantitative immunohistochemistry. RESULTS: In both non-GDM and GDM placentae, all markers, except CD86 were detected, supporting an M2-like HBC phenotype. In GDM placentae, the number of pan-macrophage (CD68), HBC-enriched (FOLR2), and M2-associated (CD163, MRC1) cells were reduced in terminal villi compared with non-GDM controls (p < 0.05; n = 13 non-GDM; n = 12 GDM), indicating reduced HBC abundance without phenotypic switching. Reduced expression of HBC-enriched (FOLR2, VSIG4) and M2-associated (CD163) transcripts supported these findings (p < 0.05; n = 18 non-GDM; n = 19 GDM). No further differences were observed following stratification by fetal growth or sex. HBC-related gene expression correlated positively with the endothelial marker PECAM1/CD31, in both non-GDM and GDM placentae (r ≥ 0.5, p < 0.05). CONCLUSIONS: HBCs abundance is reduced in GDM placentae independently of fetal growth or sex, whilst HBC phenotype is preserved. Reduced HBC abundance may contribute to placental vascular alterations that are characteristic of GDM.

Source: American Journal of Reproductive Immunology

DOI: 10.1111/aji.70216

Authors: Georgia Fakonti, Georgia Mappa, Nicolas Orsi, Eleanor M. Scott, Beth Holder, Karen Forbes

Institutions: University of Leeds, Imperial College London

Language: English

Topic: Gestational Diabetes Research and Management

Subfield: Obstetrics and Gynecology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,460